{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T11:12:06Z","timestamp":1773313926244,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","award":["785800"],"award-info":[{"award-number":["785800"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"ETH Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Precise control of the delivery of therapeutic proteins is critical for gene- and cell-based therapies, and expression should only be switched on in the presence of a specific trigger signal of appropriate magnitude. Focusing on the advantages of delivering the trigger by inhalation, we have developed a mammalian synthetic gene switch that enables regulation of transgene expression by exposure to the semi-volatile small molecule acetoin, a widely used, FDA-approved food flavor additive. The gene switch capitalizes on the bacterial regulatory protein AcoR fused to a mammalian transactivation domain, which binds to promoter regions with specific DNA sequences in the presence of acetoin and dose-dependently activates expression of downstream transgenes. Wild-type mice implanted with alginate-encapsulated cells transgenic for the acetoin gene switch showed a dose-dependent increase in blood levels of reporter protein in response to either administration of acetoin solution via oral gavage or longer exposure to acetoin aerosol generated by a commercial portable inhaler. Intake of typical acetoin-containing foods, such as butter, lychees and cheese, did not activate transgene expression. As a proof of concept, we show that blood glucose levels were normalized by acetoin aerosol inhalation in type-I diabetic mice implanted with acetoin-responsive insulin-producing cells. Delivery of trigger molecules using portable inhalers may facilitate regular administration of therapeutic proteins via next-generation cell-based therapies to treat chronic diseases for which frequent dosing is required.<\/jats:p>","DOI":"10.1093\/nar\/gkac1256","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T10:04:04Z","timestamp":1673345044000},"page":"e28-e28","source":"Crossref","is-referenced-by-count":18,"title":["Controlling therapeutic protein expression via inhalation of a butter flavor molecule"],"prefix":"10.1093","volume":"51","author":[{"given":"Adrian","family":"Bertschi","sequence":"first","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"}]},{"given":"Bozhidar-Adrian","family":"Stefanov","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"}]},{"given":"Shuai","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"}]},{"given":"Ghislaine","family":"Charpin-El\u00a0Hamri","sequence":"additional","affiliation":[{"name":"D\u00e9partement G\u00e9nie Biologique, Institut Universitaire de Technologie, Universit\u00e9 Claude Bernard , Lyon 1 Villeurbanne Cedex F-69622, France"}]},{"given":"Ana Palma","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8545-667X","authenticated-orcid":false,"given":"Martin","family":"Fussenegger","sequence":"additional","affiliation":[{"name":"Department of Biosystems Science and Engineering, ETH Zurich , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"},{"name":"University of Basel, Faculty of Science , Mattenstrasse 26, CH-4058\u00a0 Basel , Switzerland"}]}],"member":"286","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"2023031608454155800_","doi-asserted-by":"crossref","first-page":"2318","DOI":"10.1038\/s41467-018-04744-1","article-title":"Caffeine-inducible gene switches controlling experimental diabetes","volume":"9","author":"Bojar","year":"2018","journal-title":"Nat. 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